09 Nov 2000

The award for most aesthetically pleasing presentation almost certainly could go to Dr. Paul Thompson, who reviewed recent advances being made by a UCLA team in developing AD-specific brain atlases for assessing alterations in the brain over time (Abstract 110.4). The presentation was a whirlwind tour of the techniques used to develop these novel atlases and some results that point to great promise in their utility for examining dynamic changes in AD brains. As an old-time neuroanatomist, I had to struggle to keep up as phrases like "3-D vector displacement", "tensor mapping" and "warping field" flew by. But this Star Trek terminology did not obscure the stunning visual displays of brain anatomy (which I could appreciate) and the major point that focal changes in discrete brain regions can be visualized as the disease progresses.

My dumbed-down version of this elegant presentation follows: If one takes a 3-D spatial average of a group of AD brains (easier said than done, by the way), you can then use the average model for comparisons with another average model derived from either control brains or the same AD brains averaged from scans taken at a later point in time (perhaps after being on a certain treatment). This allows one to determine whether changes, e.g., atrophy, are likely to be due to random variation as opposed to the disease itself. The resulting 4-D atlas (three dimensions in space over time) can be used to examine changes in local regions such as the hippocampal formation, where initial data suggest that some focal changes might be obscured by studying the structure as a whole.

In other words, with these methods, it should be possible to monitor the rate and extent of brain changes and correlate those changes with cognitive performance and, ultimately (once postmortem data are available), histopathology. In a brief interview with him after his presentation, Dr. Thompson told me that the methods were initially developed to study changes in brain growth during development. Applying these methods to AD changes came from an interest (and presumably funding) from SmithKline Beecham, who approached Dr. Thompson with the idea of developing the AD brain atlas with the ultimate goal of being able to determine whether specific treatments are effective. The first step was to determine where, and at what rate, degenerative changes occur. In addition to being visually stunning, the results point to the possibility of establishing a means of ultimately detecting early changes that might be a harbinger of more serious pathology to come. Such early warning signals could make a critical difference in warding off the long-term pathology when effective treatments hit the market. Heady stuff? Indeed. But my bet is that this technology is where the future of AD clinical research is headed. And if this is the future, I say, "Beam me up, Scotty!"—Keith Crutcher